- Title
- Promoter methylation-regulated miR-145-5p inhibits laryngeal squamous cell carcinoma progression by targeting FSCN1
- Creator
- Gao, Wei; Zhang, Chunming; Shi, Yong; Yang, Dongli; Zhang, Ruiping; Li, Zhenyu; Cui, Jiajia; Zhang, Yuliang; Niu, Min; Li, Jun; Wu, Zhongqiang; Guo, Huina; Li, Wenqi; Xiang, Caixia; Wang, Juan; Hou, Juan; Zhang, Lu; Thorne, Rick F.; Cui, Yongping; Wu, Yongyan; Wen, Shuxin; Wang, Binquan; Li, Huizheng; Sang, Jiangwei; Zhao, Qinli; Bo, Yunfeng; Luo, Hongjie; Zheng, Xiwang; Lu, Yan
- Relation
- Molecular Therapy Vol. 27, Issue 2, p. 365-379
- Publisher Link
- http://dx.doi.org/10.1016/j.ymthe.2018.09.018
- Publisher
- Cell Press
- Resource Type
- journal article
- Date
- 2019
- Description
- Laryngeal squamous cell carcinoma (LSCC) is a common form of head and neck cancer with poor prognosis. However, the mechanism underlying the pathogenesis of LSCC remains unclear. Here, we demonstrated increased expression of fascin actin-bundling protein 1 (FSCN1) and decreased expression of microRNA-145-5p (miR-145-5p) in a clinical cohort of LSCC. Luciferase assay revealed that miR-145-5p is a negative regulator of FSCN1. Importantly, low miR-145-5p expression was correlated with TNM (tumor, node, metastasis) status and metastasis. Moreover, cases with low miR-145-5p/high FSCN1 expression showed poor prognosis, and these characteristics together served as independent prognostic indicators of survival. Gain- and loss-of-function studies showed that miR-145-5p overexpression or FSCN1 knockdown inhibited LSCC migration, invasion, and growth by suppressing the epithelial-mesenchymal transition along with inducing cell-cycle arrest and apoptosis. Additionally, hypermethylation of the miR-145-5p promoter suggested that repression of miR-145-5p arises through epigenetic inactivation. LSCC tumor growth in vivo could be inhibited by using miR-145-5p agomir or FSCN1 small interfering RNA (siRNA), which highlights the potential for clinical translation. Collectively, our findings indicate that miR-145-5p plays critical roles in inhibiting the progression of LSCC by suppressing FSCN1. Both miR-145-5p and FSCN1 are important potential prognostic markers and therapeutic targets for LSCC.
- Subject
- laryngeal squamous cell carcinoma; miR-145-5p; epithelial-mesenchymal transition; FSCN1; promoter methylation; SDG 3; Sustainable Development Goals
- Identifier
- http://hdl.handle.net/1959.13/1467889
- Identifier
- uon:47931
- Identifier
- ISSN:1525-0016
- Language
- eng
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